Stereocontrolled Synthesis of 2-Substituted-1,3-Azasilaheterocycles

Abstract

Chiral alpha-silylsulfinamides, prepared by the treatment of an alkyldiphenylsilane with lithium followed by its addition to a sulfinimine, can be applied to the synthesis of 1,3-azasilaheterocycles as derivatives of cyclic alkaloids. This synthetic route, which involves intramolecular substitution of an amino alcohol or cyclization of an amino acid promoted by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), represents a convenient means for accessing these silicon-containing heterocycles.

Reductive Lithiation and Multilithiated Compounds in Synthesis

“…The synthetic versatility of chiral α-silylsulfinamides 121, obtained as described above, was further illustrated by their employment as starting materials in the stereocontrolled synthesis of a wide array of 2-substituted-1,3-azasilaheterocycles, 122, as shown in Scheme 12.30 [57]. Application of this methodology allowed the stereocontrolled synthesis of a series of silicon-containing peptide mimics, including a potential inhibitor of the human neutrophil elastase as well as a diphenylsilane mimic of a hexapeptide fragment of the human islet amyloid polypeptide [58,59].…”

“…Following the Skrydstrup procedure [56,57], compound 124 was converted into the corresponding lithium derivative and reacted with a sulfinimine, thus affording sulfinimide 125 as a single stereoisomer. Straightforward elaboration afforded the desired silylated peptide isostere 126 in good overall yields (Scheme 12.31).…”

An efficient one-pot protocol for the synthesis of phenyl substituted 3-silatetrahydropyrans

“…Their advantages are, on the one hand, stability to air and moisture, which allows an easy handling in the synthesis and column purification steps. On the other hand, the high reactivity of the Ar-Si bond to electrophiles opens the way to a wide variety of silaheterocycles with a labile X-Si bond (X = H, Hal, HO, RO) such as silacyclohexanes, [12][13][14][15] disilacyclohexanes, 12 1,3-silapiperidine 16 and 1,4-silapiperidines. [17][18][19][20] With our continuing interest in the chemistry and conformational properties of organosilicon heterocycles, we reported previously the preparation of Si-functionalized silacyclohexane and 3-silathianes via the Ph-Si bond cleavage.…”

Synthesis and conformational properties of 1,3-dimethyl-3-phenyl-1,3-azasilinane. Low temperature dynamic NMR and computational study

“…[3][4][5][6][7][8] Recently, a renewal of interest in 1,3-azasilinanes has occurred as potential biologically active compounds. 9,10 A distinctive feature of bioactive 1,3-and 1,4-azasilinanes is the presence of aryl at silicon and that the biological activity proved to be dependent on the axial or equatorial orientation of the aryl group. The stereochemistry of the carbon analogs, geminally disubstituted 3-Me-3-Ph-piperidines has been studied by 1 Cyclic organosilicon compounds having a Ph-Si bond are of general interest from both synthetic and theoretical point of view.…”

“…1,3-azasilinanes. 10 We also prepared 3-X-3-Me-1,3-thiasilinanes (X = H, F) from 3-Me-3-Ph-1,3-thiasilinanes 12 in order to study the conformational behavior of the latter thiasilinanes 13,14 as well as of 3-Me-3-Ph-1,3-thiasilinane itself. 14 It is a general rule that monosubstituted cyclohexanes prefer the equatorial conformation because of unfavorable 1,3-diaxial interactions in the axial conformation.…”